The present invention relates to a viscose membrane, in particular to a membrane used for hemodialysis, to a process for the manufacture of the membrane, and to its use. A "viscose membrane" is a membrane comprised of regenerated cellulose and prepared from viscose.
The dialytic process and the apparatuses known as "artificial kidneys" are mainly used for the treatment of chronic kidney diseases, wherein toxic metabolites and metabolites normally contained in urine are removed from the patient's blood by means of, preferably permselective, i.e., selectively permeable, membranes. Metabolites are those compounds of the living cells which control the normal course of metabolic reactions, as well as products of metabolism formed or catabolized in human or animal organisms. Metabolites normally contained in urine are low molecular weight compounds, such as urea, creatinine, or water, and higher molecular weight compounds, such as carbohydrates and peptides, which are removed from the blood and leave the body with the urine if the kidneys are properly working.
The purpose of hemodialytic process is to transfer the toxic metabolites and the metabolites normally contained in urine, as far as possible quantitatively, out of the blood and into a rinsing fluid, especially with the aid of dissolution/diffusion processes, through the gel-like pores of a permselective membrane. The driving force for the diffusion of any diffusible substance through the membrane is the difference in concentration on each side of the membrane (diffusive permeability).
A low pressure gradient is sufficient for the permeation of water (ultrafiltration), produced by means of a higher hydrostatic pressure prevailing on the blood side of the dialyzer or a reduced pressure being applied to the dialysis side.
Besides good compatibility with blood and good wet strength, a good dialyzing capacity, i.e., permeability, is expected from a suitable dialysis membrane. For practical purposes, membranes of regenerated cellulose are preferred, while membranes of fully synthetic polymers, for example, these based on polyacrylonitrile, cellulose acetate, or polycarbonate, can be less economically manufactured on a commercial scale, and their use in the construction of dialyzers and their dialyzing capacity or wet strength in dialyzers are not satisfactory by present standards of the art.
Commercially available dialysis membranes consisting of regenerated cellulose are preferably manufactured by two fundamentally different processes, viz. either by the viscose process or by the cuprammonium process. According to the first process, a viscose solution prepared by xanthogenation is "spun", i.e., coagulated, to form sheet-like bodies of viscose gel, which are then regenerated in an acid medium to form cellulose hydrate gel, washed, desulfurized, treated with plasticizers, and dried. According to the second process, cellulose is converted by means of an aqueous ammoniacal solution ("Schweizer's Reagent") into a clear solution of a complex compound which is then coagulated to form sheet-like bodies. The cellulose is then regenerated in a suitable medium.
Due to their completely different methods of manufacture, the membranes produced by these processes differ very much in their structure, and, consequently show substantial differences in their dialytic properties.
Thus, the membranes manufactured by the cuprammonium process have the disadvantage that their molecular weight exclusion limit is restricted to about 5,000 to 10,000 Dalton, so that metabolites of medium and high molecular weight collect in the blood of the patient during dialysis. Furthermore, this process requires relatively expensive measures for recovery of the copper salts used and for purification of the membrane from copper traces. Although the known viscose membranes do not have these drawbacks, their dialyzing capacity has thus far not been satisfactory or they have only poor wet strength. Therefore, they are scarcely suitable for the purpose of hemodialysis, particularly since ultrafiltration and diffusive permeability of known dialyzing tubes made of cellulose hydrate manufactured by the viscose process are normally insufficient. By extruding very thin membranes, higher values may be obtained for the diffusive permeability, but only at the expense of wet strength--frequently also referred to as the bursting pressure--accompanied by a disproportionate increase in ultrafiltration, which is not desirable in all cases, and, above all, accompanied by serious problems of extrusion technique. Up until now, it has been impossible to achieve a suitable relation between ultrafiltration and diffusive permeability. Most of all, however, the known dialysis membranes of regenerated cellulose, i.e., both those manufactured by the viscose process as also those manufactured by the cuoxame process, sometimes display a swelling or increased area extending transversely or longitudinally to their direction of extrusion. Owing to this swelling, conventional dialyzer constructions must be provided with very expensive profiles to support the membranes, in order to keep the blood-filling volume of the apparatus as small as possible, or constant, when a transmembrane pressure is applied.
According to an article in J. Phys. Chem., 1961, 65, pages 166 to 172, commercially available dialysis membranes of regenerated cellulose are to be stretched as uniformly as possible, by hydraulic pressure, in the longitudinal and transverse directions in order to improve their dialytic properties. This means that completely finished membranes, i.e., dried membranes, are subjected to the stretching process. The permeability of these membranes, which are re-dampened and then stretched, is, however, not satisfactory. Furthermore, since the commercially available viscose membranes have different strength values in the longitudinal direction and the transverse direction, different strength values are also retained after treatment in accordance with this publication. Moreover, it is expressly stated that only limited stretching is possible.
U.S. Pat. Nos. 3,121,761 and 3,280,234 disclose flat regenerated cellulose sheets for packaging processes, to which a high strength in the longitudinal and in the transverse direction and good dimensional stability are imparted by biaxially stretching a tube of coagulated, but not yet regenerated viscose film. For this purpose, an extruded tube of viscose gel is stretched, prior to regeneration, by one and a half (11/2) to four and a half (41/2) times its original length and circumference, the strength required for a packaging film and the desired low permeability being produced by a uniform stretching of the tube in the longitudinal and in the transverse direction prior to the regeneration of the cellulose.
These patents do not contain the teaching of using these packaging films as improved hemodialysis membranes, or of causing substantial improvement of their permeation properties by applying defined stretching conditions to the films after regeneration of the cellulose. Moreover, it would be highly difficult technically to pass large-sized tubes of viscose gel, i.e., having a diameter of more than about 30 to 40 mm, through regenerating and washing baths if their thickness is less than 50 microns in the wet state.